Thin-Film Neural Interfaces with Stent-Assisted Deployment

This application is a continuation of U.S. Non-Provisional application Ser. No. 17/924,082, filed Nov. 8, 2022, which is a U.S. National Phase Application of International Application No. PCT/US 2021/025541, filed Apr. 2, 2021, which application claims priority to and the benefit of U.S. Provisional Application No. 63/035,245, filed Jun. 5, 2020, each of which are incorporated herein by reference in their entireties.

The present disclosure relates to thin-film neural interfaces, and in particular to thin-film neural interfaces with stent-assisted deployment, methods of fabricating thin-film neural interfaces incorporating a stent, and methods for delivering thin-film neural interfaces with stent-assisted deployment.

Normal neural activity is an intricate balance of electrical and chemical signals, which can be disrupted by a variety of causes (genetic, chemical or physical trauma) that affect the nervous system, causing cognitive, motor and sensory impairments. The ability to monitor brain electrical and chemical activity in real time and with noninvasive or minimally invasive techniques is important for both the understanding of nervous system functioning in health and disease and the development of effective treatment options for those disorders. Moreover, the ability to restore the diseased nervous system to an intact and normal-functioning state or substitute lost function with brain-actuated assistive devices is dependent on techniques to translate that monitoring information into effective treatment modalities, e.g., to stimulate brain tissue and modulate brain activity. One example of neuroprosthesis/brain-machine interface (BMI) and neuromodulation technology, deep brain stimulation (DBS), has proven to be effective for treatment of essential tremor disorder, Parkinson's disease, dystonia, epilepsy and psychiatric disorders such as depression, obsessive compulsive disorder and Tourette syndrome. Another example of neuroprosthesis/BMI and neuromodulation technology, brain-computer interfacing (BCI), translates specific features of signals recorded from the brain into outputs that allow the user to act on the world without the participation of peripheral nerves and muscles and has proven effective for motor rehabilitation following stroke, Parkinson's disease, and psychiatric disorders.

Neuroprosthesis/BMI and neuromodulation devices and systems tend to have a similar form factor, derived from their predecessors, e.g. the pacemaker or defibrillator. Such neuroprosthesis/BMI and neuromodulation devices and systems typically comprise an implantable, semi-implantable or external processing unit (e.g., a neurostimulator with a pulse generator, a processor with signal recorder, or the like) having electronics connected to a lead assembly that can deliver electrical pulses to or record signals from electrodes interfaced with nerves or nerve bundles via a neural interface. The lead assembly is typically formed of a conductive material and takes the form of an insulated wire connected to the neural interface via a connector on one end (e.g., a distal end) and optionally the electronics of the processing unit via another connector on another end (e.g., a proximal end). In some instances (e.g., deep implants), the lead assembly comprises additional conductors and connectors such as extension wires or a cable connected via connectors between the electrodes and the electronics of the processing unit. Neural interfaces may function as a stimulation or brain signal monitoring (and translation) device. The primary function of a BMI or, equivalently, BCI, is the monitoring of brain signals (and translation). In other words, a BMI is a neuroprosthetic system able to directly convey commands to the external world circumventing the conventional neuromuscular pathways. On the other hand, the primary function of a neurostimulation device is the recording of signals from nerves and the generation and providing of stimulation signals to nerves (sometimes in response to the recording). The brain recording and/or stimulating neuroprosthetics are often employed either for treatment of neurologic conditions and their symptoms (e.g., deep brain stimulation) or for the replacement of impaired sensory modalities (e.g., retinal implants) and may involve neuromodulation through the stimulation of nerves or brain tissue.

In various embodiments, a medical device is provided that comprises: a thin-film neural interface comprising: a first portion of a supporting structure comprised of dielectric material; a wiring layer formed on the first portion of the supporting structure; one or more electrodes formed on the first portion of the supporting structure and electrically connected to the wiring layer; and one or more encapsulation layers encasing a portion of the first portion of the supporting structure; a stent at least partially embedded in the one or more encapsulation layers, where the thin-film neural interface is helically wrapped around at least a portion of the stent; and a cable comprising: a second portion of the supporting structure comprised of the dielectric material; one or more conductive traces formed on the second portion of the supporting structure and electrically connected with the wiring layer; and the one or more encapsulation layers encasing at least a portion of the second portion of the supporting structure.

In some embodiments, the cable further comprises a polymer tube and the second portion of the supporting structure is helically wrapped around the polymer tube.

In some embodiments, the polymer tube comprises a lumen.

In some embodiments, the one or more encapsulation layers comprise a first encapsulation layer and a second encapsulation layer, the first encapsulation layer encases the portion of the first portion of the supporting structure leaving at least top surfaces of the one or more electrodes exposed, and the first encapsulation layer and the second encapsulation layer completely encase the second portion of the supporting structure.

In some embodiments, the stent is at least partially embedded in the first encapsulation layer.

In some embodiments, the dielectric material is liquid crystal polymer.

In some embodiments, the one or more encapsulation layers are comprised of polyurethane.

In some embodiments, the thin-film neural interface is helically wrapped around at least the portion of the stent such that an edge to edge distance of less than 0.5 mm is present between each turn of helixes.

In some embodiments, the second portion of the supporting structure is helically wrapped around the polymer tube such that an edge to edge distance of at least 0.5 mm is present between each turn of helixes.

In some embodiments, the cable further comprises a proximal end and a distal end, and the thin-film neural interface is disposed at the distal end of the cable.

In some embodiments, the medical device further comprises: a connector disposed at the proximal end of the cable and electrically connected to the one or more conductive traces; and a neurostimulator or computing device electrically connected with the one or more electrodes via the connector, the one or more conductive traces, and the wiring layer.

In various embodiments, a method of manufacturing a thin-film lead assembly is provided that comprises: forming a first layer of polymer on a polymer tube and a first heat shrink tube disposed on a mandrel; obtaining a thin-film structure comprising a neural interface portion and a cable portion; helically wrapping the cable portion around the polymer tube and the neural interface portion around the first heat shrink tube; forming a second layer of polymer on the cable portion; placing a second heat shrink tube over the second layer of polymer and the neural interface portion; heating the cable portion and the neural interface portion to: (i) reflow the first layer of polymer and the second layer of polymer around at least a portion of the cable portion, (ii) reflow the first layer of polymer around a portion of the neural interface portion, and (iii) recover the second heat shrink tube defining an outer diameter of the cable portion; unwrapping the neural interface portion from the first heat shrink tube; helically wrapping the neural interface portion around at least a portion of a stent; placing a third heat shrink tube over the neural interface portion; and heating the neural interface portion to: (i) reflow the first layer of polymer around at least a portion of the stent, (ii) recover the third heat shrink tube compressing the neural interface portion and the stent, and (iii) obtain the thin-film lead assembly.

In some embodiments, the method further comprises obtaining an initial structure comprising: (i) the polymer tube disposed around a first portion of the mandrel, and (ii) the first heat shrink tube disposed around a second portion of the mandrel.

In some embodiments, the neural interface portion comprises: a first portion of a supporting structure, a wiring layer formed on the first portion of the supporting structure, and one or more electrodes formed on the first portion of the supporting structure and electrically connected to the wiring layer, and where the cable portion comprises a second portion of the supporting structure, and one or more conductive traces formed on the second portion of the supporting structure and electrically connected with the wiring layer.

In some embodiments, the first portion of the supporting structure is comprised of liquid crystal polymer, the second portion of the supporting structure is comprised of liquid crystal polymer, the first layer of polymer is comprised of polyurethane, and the second layer of polymer is comprised of polyurethane.

In some embodiments, the method further comprises removing the third heat shrink tube and inserting the thin-film lead assembly into a delivery device that maintains the neural interface portion and the stent in a compressed configuration.

In some embodiments, the thin-film neural interface is helically wrapped around at least the portion of the stent such that an edge to edge distance of less than 0.5 mm is present between each turn of helixes.

In some embodiments, the cable portion is helically wrapped around the polymer tube such that an edge to edge distance of at least 0.5 mm is present between each turn of helixes.

In some embodiments, the unwrapping the neural interface portion comprises cutting through the reflowed first layer of polymer along a cut line defined by the first portion of a supporting structure, separating helixes of the neural interface portion along the cut line, and unwrapping the neural interface portion from the first heat shrink tube.

In various embodiments, a method of delivering a neural interface to a target biological structure is provided that comprises: obtaining a thin-film lead assembly comprising: a thin-film structure comprising a neural interface portion and a cable portion, where the neural interface portion comprises: a first portion of a supporting structure, one or more electrodes formed on the first portion of the supporting structure, and one or more encapsulation layers encasing a portion of the first portion of the supporting structure, and where the cable portion comprises: a second portion of the supporting structure, the one or more encapsulation layers encasing at least a portion of the second portion of the supporting structure, and a polymer tube with a lumen and the second portion of the supporting structure is helically wrapped around the polymer tube; a stent at least partially embedded in the one or more encapsulation layers, where the thin-film neural interface is helically wrapped around at least a portion of the stent; and a delivery device disposed over the thin-film lead assembly that maintains the neural interface portion and the stent in a compressed configuration; inserting a guide wire into the lumen of the thin-film lead assembly; delivering, using the guide wire, the thin-film lead assembly to the target biological structure; removing the delivery device and guide wire from the thin-film lead assembly; and deploying, using the stent, the neural interface, where the deploying comprises expanding the stent from the compressed configuration to an expanded configuration that places the one or more electrodes into contact with the target biological structure.

In some embodiments, the second portion of the supporting structure is helically wrapped around the polymer tube such that an edge to edge distance of at least 0.5 mm is present between each turn of helixes, and where the thin-film neural interface is helically wrapped around at least the portion of the stent such that an edge to edge distance of less than 0.5 mm is present between each turn of helixes.

The following disclosure describes thin-film lead assemblies and neural interfaces with stent-assisted deployment, methods of microfabricating thin-film lead assemblies and neural interfaces incorporating a stent formed on the neural interface, and stent-assisted deployment methods for delivering thin-film lead neural interfaces. As used herein, the phrases “microfabrication” and “microfabricating” refers to the process of fabricating miniature structures on micrometer scales and smaller. The major concepts and principles of microfabrication are microlithography, doping, thin-films, etching, bonding, and polishing. As used herein, the phrase “thin-films” refers to a layer of material ranging from fractions of a nanometer (monolayer) to several micrometers in thickness (e.g., between a few nanometers to about 100 μm, or the thickness of a few atoms). Thin-films may be deposited by applying a very thin film of material (e.g., between a few nanometers to about 100 μm, or the thickness of a few atoms) onto a substrate surface to be coated, or onto a previously deposited layer of thin film. In various embodiments, the thin-film lead assemblies and neural interfaces provided herein comprise a base polymer body (e.g., a supporting structure), at least one conductive trace formed on the base polymer body, a stent embedded in the base polymer body with electrodes wrapped around the stent, where the one or more electrodes are in electrical connection with the at least one conductive trace formed on the base polymer body.

Limitations associated with conventional thin-film lead assemblies and neural interfaces is that individual electrodes are manually attached to a substrate, and thus are mechanically unstable and can lead to open circuits with the neural tissue during catheter delivery or stent deployment. For example, neural interfaces that include electrodes can be manually attached to a substrate using a curable adhesive, welding, or a conductive epoxy, which are fragile and not reliable for long-term use. Materials like conductive epoxy are not biocompatible and are not suitable for long-term use. Even if the electrodes are securely attached to a substrate for long-term use in endovascular procedures, processes that involve adhesive bonding and welding are labor intensive and require manual attachment of each electrode to the substrate. Additionally, there is a desire to use smaller electrodes with higher electrode density for improved electrical stimuli. However, there are many challenges to creating such a neural interface. For example, adhesion of electrodes can degrade over time under exposure to bodily fluid, exposing an open circuit to the tissue. This ultimately results in mechanical and/or performance failure.

To address these limitations and problems, the thin-film lead assemblies and neural interfaces of various embodiments disclosed herein comprises a stent that is incorporated (e.g., embedded) in one or more layers of the supporting structure of the neural interface, where the electrode assembly (e.g., one or more electrodes in electrical connection with one or more conductive traces of the plurality of conductive traces) wraps around the stent for stent-assisted deployment of the thin-film neural interface. For example, a thin-film lead assembly may comprise a thin-film neural interface comprising: a first portion of a supporting structure comprised of dielectric material; a wiring layer formed on the first portion of the supporting structure; one or more electrodes formed on the first portion of the supporting structure and electrically connected to the wiring layer; and one or more encapsulation layers encasing a portion of the first portion of the supporting structure. The thin-film lead assembly may further comprise a stent at least partially embedded in the one or more encapsulation layers, where the thin-film neural interface is helically wrapped around at least a portion of the stent. The thin-film lead assembly may further comprise a cable comprising: a second portion of the supporting structure comprised of the dielectric material; one or more conductive traces formed on the second portion of the supporting structure and electrically connected with the wiring layer; and the one or more encapsulation layers encasing at least a portion of the second portion of the supporting structure.

In some embodiments, a method of manufacturing a thin-film lead assembly is provided that comprises: forming a first layer of polymer on a polymer tube and a first heat shrink tube disposed on a mandrel; obtaining a thin-film structure comprising a neural interface portion and a cable portion; helically wrapping the cable portion around the polymer tube and the neural interface portion around the first heat shrink tube; forming a second layer of polymer on the cable portion; placing a second heat shrink tube over the second layer of polymer and the neural interface portion; heating the cable portion and the neural interface portion to: (i) reflow the first layer of polymer and the second layer of polymer around at least a portion of the cable portion, (ii) reflow the first layer of polymer around a portion of the neural interface portion, and (iii) recover the second heat shrink tube defining an outer diameter of the cable portion; unwrapping the neural interface portion from the first heat shrink tube; helically wrapping the neural interface portion around at least a portion of a stent; placing a third heat shrink tube over the neural interface portion; and heating the neural interface portion to: (i) reflow the first layer of polymer around at least a portion of the stent, (ii) recover the third heat shrink tube compressing the neural interface portion and the stent, and (iii) obtain the thin-film lead assembly.

In some embodiments, a method of delivering a neural interface is provided that comprises: a obtaining a thin-film lead assembly comprising: a thin-film structure comprising a neural interface portion and a cable portion, where the neural interface portion comprises: a first portion of a supporting structure, one or more electrodes formed on the first portion of the supporting structure, and one or more encapsulation layers encasing a portion of the first portion of the supporting structure, and where the cable portion comprises: a second portion of the supporting structure, the one or more encapsulation layers encasing at least a portion of the second portion of the supporting structure, and a polymer tube with a lumen and the second portion of the supporting structure is helically wrapped around the polymer tube; a stent at least partially embedded in the one or more encapsulation layers, where the thin-film neural interface is helically wrapped around at least a portion of the stent; and a delivery device disposed over the thin-film lead assembly that maintains the neural interface portion and the stent in a compressed configuration; inserting a guide wire into the lumen of the thin-film lead assembly; delivering, using the guide wire, the thin-film lead assembly to the target biological structure; removing the delivery device and guide wire from the thin-film lead assembly; and deploying, using the stent, the neural interface, where the deploying comprises expanding the stent from the compressed configuration to an expanded configuration that places the one or more electrodes into contact with the target biological structure.

Advantageously, these approaches provide a thin-film neural interface, which has improved adhesion between the stent and the electrodes, a smaller footprint, and greater design flexibility. This solution is scalable to interface multiple electrodes with tissue using thin film substrates, and thus enabling several therapeutic opportunities for neurostimulation. Furthermore even for applications where multiple electrodes are not required, various embodiments can be miniaturized to make the implant minimally invasive, additionally may make invasive anatomies to become accessible (or navigable) due to the miniaturization. It should be understood that although deep brain neurostimulation are provided as examples of some embodiments, this solution is applicable to all interfaces, leads, and devices that need electrodes/sensors interfaced with tissue.

1 FIG. 1 FIG. 100 100 105 110 105 105 115 120 125 130 135 105 115 115 105 120 115 115 120 115 115 125 115 135 135 130 135 shows a neurostimulation/BMI systemin accordance with some aspects of the present disclosure. In various embodiments, the neurostimulation/BMI systemincludes a computing deviceand a thin-film lead assembly. In various embodiments, the computing devicecan be implantable, semi-implantable, or an external system. The computing devicemay include a housing, a feedthrough assembly, a power source, an antenna, and an electronics module. For applications where the computing deviceis implanted, the housingmay be comprised of materials that are biocompatible such as bioceramics or bioglasses for radio frequency transparency, or metals such as titanium. In some embodiments, the size and shape of the housingmay be selected such that the computing devicecan be implanted within a patient. In the example shown in, the feedthrough assemblyis attached to a hole in a surface of the housingsuch that the housingis hermetically sealed. The feedthrough assemblymay include one or more feedthroughs (i.e., electrically conductive elements, pins, wires, tabs, pads, etc.) mounted within and extending through the surface of the housingor a cap from an interior to an exterior of the housing. The power sourcemay be within the housingand connected (e.g., electrically connected) to the electronics moduleto power and operate the components of the electronics module. The antennamay be connected (e.g., electrically connected) to the electronics modulefor wireless communication with external devices via, for example, radiofrequency (RF) telemetry.

135 120 135 110 120 135 135 140 145 140 140 150 140 145 In some embodiments, the electronics modulemay be connected (e.g., electrically connected) to interior ends of the feedthrough assemblysuch that the electronics moduleis able to apply a signal or electrical current to conductive traces of the thin-film lead assemblyconnected to exterior ends of the feedthrough assembly. The electronics modulemay include discrete and/or integrated electronic circuit components that implement analog and/or digital circuits capable of producing the functions attributed to the neuromodulation or BMI devices or systems such as applying neural stimulation to a patient or sensing and recording electrical activity from a patient. In various embodiments, the electronics modulemay include software and/or electronic circuit components such as a pulse generatorthat generates a signal to deliver a voltage, current, optical, or ultrasonic stimulation to a nerve or artery/nerve plexus via electrodes, a controllerthat determines or senses electrical activity and physiological responses via the electrodes and sensors, controls stimulation parameters of the pulse generator(e.g., control stimulation parameters based on feedback from the physiological responses), causes delivery of the stimulation via the pulse generatorand electrodes, and/or records the determined or sensed electrical activity in a storage device, and a memorywith program instructions operable on by the pulse generatorand the controllerto perform one or more processes for: (i) applying or delivering neural stimulation, or (ii) translating neuronal information into commands capable of controlling external software or hardware such as a computer or robotic arm.

110 155 160 160 162 160 155 160 170 155 170 175 162 180 180 162 175 175 162 135 In various embodiments, the thin-film lead assemblyis a monolithic structure that includes a cableor lead body and a thin-film neural interface. In some embodiments, the thin-film neural interface(e.g., an electrode assembly) comprises a thin-film structure having one or more electrodes(i.e., recording electrodes, neurostimulation electrodes, sensors, or combinations thereof) wrapped around a stent 165. In some embodiments, the thin-film neural interfaceis formed at a distal end of the cable. The thin-film neural interfacemay be formed from the same supporting structureas the cable. The supporting structureincludes a base dielectric material such as a polymer having suitable dielectric, flexibility and biocompatibility characteristics that provides support for microelectronic structures including conductive traces, electrodes, wiring layers, optional contacts, etc. The wiring layermay be used to directly or indirectly electrically connect the electrodeswith the one or more conductive traces. The conductive tracesmay be used to directly or indirectly electrically connect the electrodeswith the electronics module. The term “directly”, as used herein, may be defined as being without something in between. The term “indirectly”, as used herein, may be defined as having something in between.

110 185 185 155 135 105 120 185 155 135 105 105 155 185 In some embodiments, the thin-film lead assemblyfurther includes a connector. In certain embodiments, the connectoris bonding material that bonds conductor material of the cableto the electronics moduleof the device(e.g., the neurostimulator) via the feedthrough assembly. The bonding material may be a conductive epoxy or a metallic solder or weld such as platinum. In other embodiments, the connectoris conductive wire, conductive traces, or bond pads (e.g., a wire, trace, or bond pads formed of a conductive material such as copper, silver, or gold) formed on a substrate and bonds a conductor of the cableto the electronics moduleof the device. In alternative embodiments, the deviceand the cableare designed to connect with one another via a mechanical connectorsuch as a pin and sleeve connector, snap and lock connector, flexible printed circuit.

2 2 FIGS.A andB 1 FIG. 200 110 200 205 210 205 205 215 220 210 220 205 show a thin-film lead assembly(e.g., the thin-film lead assemblydescribed with respect to) in accordance with aspects of the present disclosure. In various embodiments, the thin-film lead assemblycomprises a cableand a thin-film neural interfaceelectrically connected to the cable. The cablehas a proximal endand a distal end. As used herein, the term “proximal end” refers to a first end of the cable, while the term “distal end” refers to a second end opposing the first end. For example, the proximal end may be an end of the cable, which is closest to the user, and the distal end may be an end of the cable, which is furthest from the user. In some embodiments, the thin-film neural interfaceis disposed at the distal endof the cable.

205 225 230 225 225 215 220 225 225 The cablemay comprise a supporting structureand one or more conductive tracesformed on a portion of the supporting structure. As used herein, the term “formed on” refers to a structure or feature that is formed on a surface of another structure or feature, a structure or feature that is formed within another structure or feature, or a structure or feature that is formed both on and within another structure or feature. In some embodiments, the supporting structureextends from the proximal endto the distal end. The supporting structureis made of one or more layers of dielectric material (i.e., an insulator). The dielectric material may be selected from the group of electrically nonconductive materials consisting of organic or inorganic polymers, ceramics, glass, glass-ceramics, polyimide-epoxy, epoxy-fiberglass, and the like. For example, the dielectric material may be a polymer of imide monomers (i.e., a polyimide), a liquid crystal polymer (LCP) such as Kevlar®, parylene, polyether ether ketone (PEEK), or combinations thereof. In certain instances, the supporting structurecomprises one or more layers of LCP.

225 215 220 225 225 In various embodiments, the supporting structurehas a thickness (t) from the proximal endto the distal end. In some embodiments, the thickness (t) is from 10 μm to 950 μm, for example about 150 μm or about 500 μm. As used herein, the terms “substantially,” “approximately,” and “about” are defined as being largely but not necessarily wholly what is specified (and include wholly what is specified) as understood by one of ordinary skill in the art. In any disclosed embodiment, the term “substantially,” “approximately,” or “about” may be substituted with “within [a percentage] of” what is specified, where the percentage includes 0.1, 1, 5, and 10 percent. In some embodiments, the supporting structurehas a length (l) of 5 cm to 150 cm or 50 cm to 100 cm, e.g., about 75 cm. In some embodiments, the supporting structurehas a width (w) from a first side to a second side. In some embodiments, the width (w) is from 0.5 mm to 5 mm, for example about 0.6 mm or about 4 mm.

230 230 230 230 225 In various embodiments, the one or more conductive tracesare a plurality of traces, for example, two or more conductive traces or from two to forty-eight conductive traces (e.g., one conductive trace for each electrode/sensor). The plurality of conductive tracesare comprised of one or more layers of conductive material. The conductive material selected for the one or more conductive tracesshould have good electrical conductivity and may include pure metals, metal alloys, combinations of metals and dielectrics, and the like. For example, the conductive material may be copper (Cu), gold (Au), silver (Ag), gold/chromium (Au/Cr), etc. In some embodiments, it is also desirable that the conductive material selected for the one or more conductive traceshave thermal expansion characteristics or a coefficient of thermal expansion (CTE) that is approximately equal to that of CTE of the supporting structure. Matching the CTE of components that contact one another is desirable because it eliminates the development of thermal stresses, which may occur during fabrication and the operation of the cable, and thus eliminates a known cause of mechanical failure in the components.

230 225 230 225 225 230 225 230 215 220 230 The one or more conductive tracesmay be deposited onto a surface of the supporting structureby using thin film deposition techniques well known to those skilled in the art such as by sputter deposition, chemical vapor deposition, metal organic chemical vapor deposition, electroplating, electroless plating, and the like. In some embodiments, the thickness of the one or more conductive tracesis dependent on the particular impedance desired for conductor, in order to ensure excellent signal integrity (e.g., electrical signal integrity for stimulation or recording). For example, if a conductor having a relatively high impedance is desired, a small thickness of conductive material should be deposited onto the supporting structure. If, however, a signal plane having a relatively low impedance is desired, a greater thickness of electrically conductive material should be deposited onto the supporting structure. In certain embodiments, each of the one or more conductive traceshas a thickness (d). In some embodiments, the thickness (d) is from 0.5 μm to 100 μm or from 25 μm to 50 μm, for example about 25 μm or about 40 μm. In some embodiments, each of the one or more conductive traceshas a length (m) of about 5 cm to 200 cm or 50 cm to 150 cm, e.g., about 80 cm. In certain embodiments, each of the one or more conductive tracesextends from the proximal endto the distal end. In some embodiments, each of the one or more conductive traceshas a width (y) from 2.0 μm to 500 μm , for example about 30 μm or about 50 μm .

205 235 235 225 230 235 225 230 235 The cablemay further comprise a base tube. The base tubemay comprise a medical grade polymer material. In certain instances, the medical grade polymer is a soft polymer such as silicone. The supporting structureand conductive tracesmay be helically wrapped around the base tube. As used herein, the phrases “helical” or “helically wrapped” refer to a device fabricated with plural helixes or helices, which are a type of smooth space curve, i.e. a curve in three-dimensional space. The helixes may be wrapped in a clockwise direction or anti-clockwise direction. The helixes have the property that a tangent line at any point makes a constant angle with a fixed line called the axis. In some instances, the supporting structureand conductive tracesare wrapped loosely around the base tube. The “wrapped loosely” configuration means that the turns are loosely packed with an edge to edge distance of at least 0.5 mm between each turn of the helixes.

205 240 240 225 230 240 The cablemay further comprise one or more encapsulation layers. The one or more encapsulation layersmay completely encase at least a portion of the supporting structureand the one or more conductive traces. The one or more encapsulation layersmay be comprised of a medical grade polymer material. In some embodiments, the medical grade polymer is thermosetting plastic or thermoplastic. For example, the medical grade polymer may be a soft polymer such as silicone, a polymer dispersion such as latex, a chemical vapor deposited poly(p-xylylene) polymer such as parylene, or a polyurethane such as Bionate® Thermoplastic Polycarbonate-urethane (PCU) or CarboSil® Thermoplastic Silicone-Poly carbonate-urethane (TSPCU).

210 225 240 245 240 225 250 255 225 205 225 210 200 255 250 230 255 230 230 225 225 255 250 The thin-film neural interfacecomprises a supporting structure′, one or more encapsulation layers′, and a stentembedded at least partially within the one or more encapsulation layers′. As used herein, “embedded at least partially” means at least 30% of an object (in this instance the stent) is embedded within the other object (in this instance the one or more encapsulation layers). The supporting structure′ provides support for microelectronic structures including one or more electrodes, a wiring layer, and optional contact(s). In various embodiments, the supporting structureof the cableand the supporting structure′of the thin-film neural interfaceare the same structure (i.e., the supporting structure is continuous through the thin-film lead assembly), which creates a monolithic thin-film lead assembly. The wiring layerelectrically connects each of the one or more electrodesto the one or more conductive traces. In some instances, the wiring layermay be formed continuously with the one or more conductive traces. For example, each of the one or more conductive tracesmay extend from the supporting structurethrough the supporting structure′ (as the wiring layer) and terminate at one or more of the electrodes.

240 205 240 210 200 240 210 250 250 240 210 240 205 In some embodiments, the one or more encapsulation layersof the cableand the one or more encapsulation layers′ of the thin-film neural interfaceare the same structure (i.e., the encapsulation layer is continuous through the thin-film lead assembly), which creates a monolithic thin-film lead assembly. However, the one or more encapsulation layers′ of the thin-film neural interfaceare not disposed over at least a top surface of the one or more electrodessuch that the one or more electrodescan directly interface with a biological structure. Consequently, the one or more encapsulation layers′ of the thin-film neural interfacemay have less layers of material (e.g., polymer) as compared to the one or more encapsulation layersof the cable.

245 245 250 250 245 200 245 245 200 245 245 2 2 FIGS.A andB 7 7 FIGS.A andB In some embodiments, the stentcomprises a mesh framework that is collapsible and expandable, as shown in. The stentcan include any mechanical framework or scaffolding that positions the one or more electrodeswithin a body lumen, such as a vessel, and facilitates interfacing the one or more electrodeswith a biological structure such as tissue or fluid. For example, the stentmay be collapsed during insertion of the thin-film lead assemblyin a subject (e.g., a human patient), and the stentmay expand to take the shape of a surrounding body lumen when deployed in the subject. In certain instances, the stentmay be adapted to expand when deployed out of an end of a delivery device such as a sheath disposed around the thin-film lead assembly(see, e.g.,). Additionally, the stentmay be adapted to contract when retracted into the end of the delivery device. Thus, the stentmay be adapted to be deployed, retrieved, and re-deployed. The redeployment may take place at a different region within the subject to that of the earlier deployment.

245 245 245 245 245 The stentis made of an inert material, which can remain functional in the body for long periods of time (e.g., several months to years). For example, the stentmay be laser cut or woven from the inert material in any suitable shape, e.g., a column or tube. In some embodiments, the stentis a mesh tube made of medical-grade metal such as stainless steel or cobalt alloy metal, which fits into a biological structure and expands radially against the walls of the biological structure. In other embodiments, the stentis a self-expanding (e.g., temperature sensitive) mesh tube made of medical-grade “smart metals.” For example, the stentmay be made of stainless steel, platinum, or shape memory alloys containing nickel and titanium (e.g., nitinol). Shape memory alloys refer to alloys that retain their original shape when exposed to certain conditions (e.g., temperature or pressure). These stents are designed to contract or expand under certain conditions (e.g., contract in cold temperature and expand or return to their original shape under warm temperatures).

225 245 225 245 250 245 210 250 225 250 245 250 245 210 245 250 The supporting structure′ and microelectronic structures may be helically wrapped around the stent. The helixes may be wrapped in a clockwise direction or anti-clockwise direction. In some instances, the supporting structure′ and microelectronic structures are wrapped tightly around the stent. The “wrapped tightly” configuration means that the turns are tightly packed with an edge to edge distance of less than 0.5 mm between each turn of the helixes. The one or more electrodesare wrapped around the stentfor stimulating and/or sensing activity of biological structures such as tissue and/or fluid proximal to the thin-film neural interface. The one or more electrodesmay be arranged in any suitable configuration on the supporting structure′ such that the one or more electrodestake on any suitable arrangement wrapped around the stent. For example, the one or more electrodescan be arranged as follows: sinusoidal arrangement of electrodes; spiral arrangement of electrodes to enable 360° contact of the electrodes to the wall of a vessel once deployed; and a dense arrangement of electrodes for increased coverage. In some embodiments, the stentis laser cut or woven in a manner such that there is additional material or markers where the thin-film neural interfacecan wrap around the stentto assist with electrical connection stability of the one or more electrodesand uniformity of electrode locations.

While the thin-film lead assembly has been described at some length and with some particularity with respect to a specific design and/or performance need, it is not intended that the thin-film lead assembly be limited to any such particular design and/or performance need. Instead, it should be understood the thin-film lead assembly described herein is an exemplary embodiment, and that the thin-film lead assembly is to be construed with the broadest sense to include variations of the specific design and/or performance need described herein, as well as other variations that are well known to those of skill in the art. In particular, the shape and location of components and layers in the thin-film lead assembly may be adjusted or modified to meet specific design and/or performance needs. Furthermore, it is to be understood that other structures have been omitted from the description of the thin-film lead assembly for clarity. The omitted structures may include sensor structures, insulating layers, interconnect components, passive devices, etc.

3 FIG.A 2 2 FIGS.A andB 3 300 300 305 310 315 305 320 325 330 335 305 305 305 310 315 305 225 320 325 (top view) andB (cross-sectional view) show a thin-film neural interfacewith stent-assisted deployment (e.g., the neural interface described with respect to) in accordance with aspects of the present disclosure. The thin-film neural interfacecomprises a supporting structurehaving a proximal endand a distal end. The supporting structurecomprises a front side, a back side, and opposing edges,. In some embodiments, the supporting structureis made of one or more layers of dielectric material (i.e., an insulator). The dielectric material may be selected from the group of electrically nonconductive materials consisting of organic or inorganic polymers, ceramics, glass, glass-ceramics, polyimide-epoxy, epoxy-fiberglass, and the like. In certain embodiments, the dielectric material is a polymer of imide monomers (i.e., a polyimide), a liquid crystal polymer (LCP) such as Kevlar®, parylene, polyether ether ketone (PEEK), or combinations thereof. In certain instances, the supporting structurecomprises one or more layers of LCP. The supporting structurehas a width (w) from the proximal endto the distal end. In some embodiments, the width (w) is from 0.01 mm to 3 mm, for example about 0.08 mm or about 0.5 mm. In some embodiments, the supporting structurehas a length (l) of 1 mm to 20 cm or 1 mm to 50 mm, e.g., about 10 mm. In some embodiments, the supporting structurehas a thickness (t) from the front sideto the back side. In some embodiments, the thickness (t) is from 10 μm to 950 μm, for example about 150 μm or about 500 μm 0.

300 345 350 355 345 305 345 305 345 305 345 345 355 305 345 350 355 The thin-film neural interfacefurther comprises one or more electrodesin electrical connection with a wiring layerdirectly or via optional contacts. The one or more electrodesare formed on the supporting structure. In some embodiments, the top surface of the one or more electrodesis coplanar with the top surface of the supporting structure. In other embodiments, the top surface of the one or more electrodesis raised above the top surface of the supporting structure. The one or more electrodesmay be comprised of conductive material such as copper (Cu), gold (Au), silver (Ag), gold/chromium (Au/Cr), platinum (Pt), platinum/iridium (Pt/Ir), titanium (Ti), gold/titanium (Au/Ti), or any alloy thereof, for example. The one or more electrodesmay have a thickness (z) of from 0.1 um to 50 μm, from 0.3 μm to 30 μm, from 0.5 μm to 20 μm, or from 1 μm to 15 μm. In certain embodiments, the contact(s)are formed on the supporting structureand provide electrical contact between the one or more electrodesand the wiring layer. The contact(s)may be comprised of conductive material such as copper (Cu), gold (Au), silver (Ag), gold/chromium (Au/Cr), platinum (Pt), platinum/iridium (Pt/Ir), titanium (Ti), gold/titanium (Au/Ti), or any alloy thereof, for example.

350 305 350 357 350 350 305 350 305 350 305 350 305 The wiring layermay be formed on the supporting structure. In various embodiments, the wiring layeris formed continuously with the one or more conductive tracesof the cable, and is comprised of various metals or alloys thereof, for example, copper (Cu), gold (Au), silver (Ag), gold/chromium (Au/Cr), platinum (Pt), platinum/iridium (Pt/Ir), titanium (Ti), gold/titanium (Au/Ti), or any alloy thereof. The wiring layermay have a thickness (x) of from 0.5 μm to 100 μm, from 0.5 μm to 15 μm, from 0.5 μm to 10 μm, or from 0.5 μm to 5 μm. In some embodiments, a top surface of the wiring layeris coplanar with a top surface of the supporting structure. In other embodiments, the wiring layeris embedded within the supporting structure. In yet other embodiments, the wiring layeris formed on the top surface of the supporting structureand the top surface of the wiring layeris raised above the top surface of the supporting structure.

300 360 305 360 325 330 335 360 330 335 320 360 345 360 The thin-film neural interfacefurther comprises one or more encapsulation layersformed on at least a portion of the supporting structure. The one or more encapsulation layersare formed on the back sideand wrap around over the opposing edges,. In some instances, the one or more encapsulation layersmay further wrap around over the opposing edges,to the front side. However, the one or more encapsulation layersdo not cover the top surface of the one or more electrodes. The one or more encapsulation layersmay be comprised of a medical grade polymer material. In some embodiments, the medical grade polymer is thermosetting plastic or thermoplastic. For example, the medical grade polymer may be a soft polymer such as silicone, a polymer dispersion such as latex, a chemical vapor deposited poly(p-xylylene) polymer such as parylene, or a polyurethane such as Bionate® Thermoplastic Polycarbonate-urethane (PCU) or CarboSil® Thermoplastic Silicone-Poly carbonate-urethane (TSPCU)

300 365 360 365 360 365 360 360 365 360 345 365 345 365 345 365 The thin-film neural interfacefurther comprises a stentembedded within the one or more encapsulation layers. Specifically, some or all of the stentis at least partially embedded within the one or more encapsulation layers. The stentmay be embedded within the one or more encapsulation layersvia reflow of the one or more encapsulation layers, as described in detail herein. Advantageously, the stentbeing embedded within the one or more encapsulation layersattaches the one or more electrodesto the stentsuch that the one or more electrodesmove with the stentas it expands and collapses. This avoids having to manually attach the one or more electrodesto the stentusing a curable adhesive, welding, or a conductive epoxy, which are fragile and not reliable for long-term use.

4 4 FIGS.A-E 1 2 2 3 3 FIGS.,A,B,A, andB 400 400 show structures and respective processing steps for fabricating a thin-film structure(e.g., a portion of the thin-film lead assembly as described with respect to) in accordance with various embodiments. It should be understood by those of skill in the art that thin-film structurecan be manufactured in a number of ways using a number of different tools. In general, however, the methodologies and tools used to form the structures of the various embodiments can be adopted from integrated circuit (IC) technology. For example, the structures of the various embodiments, e.g., supporting structure, conductive traces, electrodes, sensors, wiring layers, bond/contact pads, etc., may be built with or without a substrate and realized in films of materials patterned by photolithographic processes. In particular, the fabrication of various structures described herein may typically use three basic building blocks: (i) deposition of films of material on a substrate and/or previous film(s), (ii) applying a patterned mask on top of the film(s) by photolithographic imaging, and (iii) etching the film(s) selectively to the mask.

As used herein, the term “depositing” may include any known or later developed techniques appropriate for the material to be deposited including but not limited to, for example: chemical vapor deposition (CVD), low-pressure CVD (LPCVD), plasma-enhanced CVD (PECVD), semi-atmosphere CVD (SACVD) and high density plasma CVD (HDPCVD), rapid thermal CVD (RTCVD), ultra-high vacuum CVD (UHVCVD), limited reaction processing CVD (LRPCVD), metalorganic CVD (MOCVD), sputtering deposition, ion beam deposition, electron beam deposition, laser assisted deposition, thermal oxidation, thermal nitridation, spin-on methods, physical vapor deposition(PVD), atomic layer deposition (ALD), chemical oxidation, molecular beam epitaxy (MBE), plating (e.g., electroplating), or evaporation.

4 FIG.A 405 410 410 410 410 410 shows a supporting structure comprising a first polymer layeroverlying an optional substrate(e.g., a backer). In various embodiments, the supporting structure may be provided, obtained, or fabricated as a single wafer or panel. The substratemay be comprised of any type of metallic or non-metallic material. For example, the substratemay be comprised of but not limited to silicon, germanium, silicon germanium, silicon carbide, and those materials consisting essentially of one or more Group III-V compound semiconductors having a composition defined by the formula A1X1GaX2InX3AsY1PY2NY3SbY4, where X1, X2, X3, Y1, Y2, Y3, and Y4 represent relative proportions, each greater than or equal to zero and X1+X2+X3+Y1+Y2+Y3+Y4=1 (1 being the total relative mole quantity). Substratemay additionally or alternatively be comprised of Group II-VI compound semiconductors having a composition ZnA1CdA2SeB1TeB2, where A1, A2, B1, and B2 are relative proportions each greater than or equal to zero and A1+A2+B1+B2=1 (1 being a total mole quantity). The processes to provide, obtain, or fabricate substrate, as illustrated and described, are well known in the art and thus, no further description is provided herein.

405 405 410 410 405 405 405 The first polymer layermay be comprised of one or more layers of dielectric material (i.e., an insulator). The dielectric material may be selected from the group of electrically nonconductive materials consisting of organic or inorganic polymers, ceramics, glass, glass-ceramics, polyimide-epoxy, epoxy-fiberglass, and the like. In certain embodiments, the dielectric material is a polyimide, polyurethane, a LCP, parylene, a PEEK, or combinations thereof. The forming of the first polymer layermay include depositing and curing a dielectric material directly on the substratewithout an adhesion promoter. For example, a solution comprised of an imidizable polyamic acid compound dissolved in a vaporizable organic solvent without an adhesion promoter may be deposited (e.g., spin coated) onto the substrate. The solution may then be heated at a temperature, preferably less than 250° C., to imidize the polyamic acid compound to form the desired polyimide and vaporize the solvent. The first polymer layermay then be thinned to a desired thickness by planarization, grinding, wet etch, dry etch, oxidation followed by oxide etch, or any combination thereof. This process can be repeated to achieve a desired thickness for the first polymer layer. In some embodiments, the first polymer layermay have a thickness from 10 μm to 300 μm.

4 4 4 FIGS.A,B andC 4 4 FIGS.A andB 411 412 400 415 411 405 415 405 405 405 show forming a cable portionand neural interface portionof the thin-film structure. Specifically,show conductive tracesformed in a pattern on the cable portionof the first polymer layer. In some embodiments, forming the conductive tracesmay include depositing a seed layer (e.g., a copper (Cu) seed layer, a gold (Au) seed layer, a silver (Ag) seed layer, a gold/chromium (Au/Cr) seed layer, platinum (Pt) seed layer, platinum/iridium (Pt/Ir) seed layer, etc.) over the first polymer layer. The seed layer may be configured to enable forming of a conductive trace on the first polymer layer(e.g., through Cu electroplating, Au electroplating, Sn electroplating, Ag electroplating, Au/Cr electroplating, platinum (Pt) electroplating, platinum/ iridium (Pt/Ir) electroplating, etc.). Optionally, and prior to forming of the seed layer, an adhesion layer may be deposited over the first polymer layerto enable adequate application of the seed layer. Deposition of either or both of the adhesion layer and seed layer may include sputter deposition

405 405 415 405 415 405 415 405 415 405 400 Following deposition of the seed layer, a resist pattern may be formed above the first polymer layer. The resist pattern may include openings that align over at least a portion of the first polymer layerfor forming of a plurality of conductive traces(e.g., a conductive layer with a cross-sectional thickness of 0.5 μm to 100 μm or from 25 μm to 50 μm) on the first polymer layer. For example, the resist may be patterned with openings to form: (i) a first conductive traceover a first region of the first polymer layer, (ii) a second conductive traceover a second region of the first polymer layer, and (iii) a third conductive traceover a third region of the first polymer layer. It should be understood by those of skill in the art that different patterns and shapes are also contemplated by the present disclosure to maximize the length of the thin-film structure.

415 405 405 415 405 2 2 2 2 In various embodiments, the conductive tracesmay be deposited through electroplating (e.g., through Cu electroplating, Au electroplating, Sn electroplating, Ag electroplating, Au/Cr electroplating, etc.) and may be positioned over at least a portion of the first polymer layer(e.g., the first region, the second region, and the third region). The electroplating maybe performed at a current density of about 4.0 mA/cm2 to about 4.5 mA/cm2 . In some embodiments, the exposed area or portion of the first polymer layermay encompass about 8 cmto about 10 cm. The current may be about 14 mA to about 18 mA and the duration may be from about 110 minutes to about 135 minutes to form the conductive traceshaving a thickness of about 8 μm to about 10 μm. In other embodiments, the exposed area or portion of the first polymer layermay encompass about 10 cmto about 18 cm. The current may be about 18 mA to about 28 mA and the duration may be from about 35 minutes to about 50 minutes to form the wiring layer having a thickness of about 2 μm to about 5 μm.

415 415 405 Following the deposition of the conductive traces, the intermediate structure may be subjected to a strip resist to remove the resist pattern and expose portions of the seed layer (portions without wire formation), and optionally the adhesion layer. The exposed portions of the seed layer, and optionally the adhesion layer, may then be subjected to an etch (e.g., wet etch, dry etch, etc.) to remove those portions, thereby isolating the conductive tracesover at least a portion of the first polymer layer.

4 FIG.C 420 415 405 420 420 405 420 415 405 420 420 420 shows an optional second polymer layerformed over the conductive tracesand the first polymer layer. The second polymer layermay be comprised of dielectric material (i.e., an insulator). The dielectric material may be selected from the group of electrically nonconductive materials consisting of organic or inorganic polymers, ceramics, glass, glass-ceramics, polyimide-epoxy, epoxy-fiberglass, and the like. In certain embodiments, the dielectric material is a polyimide, a LCP, silicone, parylene, a PEEK, or combinations thereof. The second polymer layermay be comprised of the same material or a different material from that of the first polymer layer. The forming of the second polymer layermay include depositing and curing of a polymer material directly on the conductive tracesand the first polymer layer. The second polymer layermay then be thinned to a desired thickness by planarization, grinding, wet etch, dry etch, oxidation followed by oxide etch, or any combination thereof. This process can be repeated to achieve a desired thickness for the second polymer layer. In some embodiments, the second polymer layermay have a thickness from 10 μm to 300 μm.

422 420 422 420 422 405 420 405 420 422 In various embodiments, a third polymer layermay be formed over the second polymer layer. In some embodiments, the third polymer layeris only formed over a portion of the second polymer layer. The third polymer layermay be comprised of dielectric material (i.e., an insulator). The dielectric material may be selected from the group of electrically nonconductive materials consisting of organic or inorganic polymers, ceramics, glass, glass-ceramics, polyimide-epoxy, epoxy-fiberglass, and the like. In some embodiments, the dielectric material is a polyimide, a LCP, silicone, parylene, a PEEK, or combinations thereof. The third polymer layer may be comprised of the same material or a different material from that of the first polymer layerand the second polymer layer. In some embodiments, the first polymer layercomprises LCP, the second polymer layercomprises LCP, and the third polymer layercomprises LCP.

400 412 412 400 415 412 425 405 420 425 415 415 425 415 425 415 4 4 FIGS.B-F 4 FIG.A 4 4 FIGS.A andB 4 4 FIGS.B andC In various embodiments, the thin-film structuremay further comprise one or more additional supporting structures that may support one or more additional electronic structures of the neural interface portionsuch as an electrode, sensor, conductor, and/or connector.show forming the neural interface portionof the thin-film structureon the supporting structure formed inthat is electrically connected to the conductive tracesformed in. As shown in, forming the neural interface portioncomprises forming a wiring layerin a pattern on the first polymer layerand/or the second polymer layer. The wiring layermay be formed at the same time as forming the conductive traces, or may be formed subsequent to forming the conductive traces. For example, the wiring layerand the conductive tracesmay be deposited as a continuous layer of conductive material, or may be deposited as two separate metallization layers of conductive material that are in electrical contact with one another. The wiring layermay be formed in the same manner as described in detail with respect to the conductive traces.

412 420 422 425 405 420 420 405 In some embodiments, forming the neural interface portionfurther comprises forming the second polymer layerand/or the third polymer layerover the wiring layerand the first polymer layer. As described herein, the second polymer layermay be comprised of dielectric material (i.e., an insulator) selected from the group of electrically nonconductive materials consisting of organic or inorganic polymers, ceramics, glass, glass-ceramics, polyimide-epoxy, epoxy-fiberglass, and the like. In certain embodiments, the dielectric material is a polyimide, a LCP, parylene, silicone, a PEEK, or combinations thereof. The second polymer layermay be comprised of the same material or a different material from that of the first polymer layer.

4 FIG.D 4 FIG.E 4 FIG.E 412 430 420 422 425 430 435 440 430 425 435 440 420 430 425 435 435 435 420 435 425 435 435 445 420 As shown in, forming the neural interface portionfurther comprises forming contact viasin the second polymer layeror the third polymer layerto the wiring layer. The contact viascan e.g. be formed using conventional lithographic, etching, and cleaning processes, known to those of skill in the art.shows electrodes (optionally one or more sensors)and contactsformed on and within the contact viasto the portion of the top surface the wiring layer. In various embodiments, the electrodes(optionally one or more sensors) and contactsmay be formed using conventional processes. For example, a conductive material may be blanket deposited on the second polymer layer, including within the contact viasand in contact with the portion of the top surface the wiring layer. The conductive material may be copper (Cu), gold (Au), silver (Ag), gold/chromium (Au/Cr), platinum (Pt), platinum/iridium (Pt/Ir), titanium (Ti), gold/titanium (Au/Ti), or any alloy thereof, for example. Once the conductive material is deposited, the conductive material may be patterned using conventional lithography and etching processes to form at least one electrodeor a pattern of electrodesas shown in, for example. In some embodiments, at least one electrodeis formed on the second polymer layersuch that the at least one electrodeis in electrical contact with at least a portion of a top surface of the wiring layer. In some embodiments, the pattern of electrodesmay include each electrodespaced apart from one another via a portion or regionof the second polymer layer. It should be understood by those of skill in the art that different patterns are also contemplated by the present disclosure.

4 FIG.F 400 405 415 425 420 435 440 410 400 410 435 420 shows the thin-film structureincluding the first polymer layer, the conductive traces, the wiring layer, the second polymer layer, the electrodes, and the contactsdetached from the substrate. In some embodiments, detaching the thin-film structurefrom the substratemay include removal of the substrate (e.g., selective etching), and cleaning (e.g., a step-wise rinsing process) at least top surfaces of the electrodesand the second polymer layerwith acetone, isopropyl alcohol, non-ionic surfactant, a liquid detergent system, and/or deionized water to remove residual material such as remaining adhesive material.

5 5 FIGS.A-J 1 2 2 3 3 4 4 FIGS.,A,B,A,B, andA-F 5 FIG.A 500 505 505 510 515 520 510 510 520 505 525 530 520 525 525 520 show cross-sectional views of the structures and respective processing steps for fabricating a thin-film lead assemblyand structures thereof described in.shows a beginning structurefor a thin-film lead assembly. The beginning structurecomprises a polymer tubedisposed around a first portionof a mandrel. The polymer tubeis comprised of a medical grade polymer material, for example, a soft polymer such as silicone. The polymer tubecovers a region of the mandrelupon which the cable of the thin-film lead assembly is to be formed. The beginning structurefurther comprises a first heat shrink tubedisposed around a second portionof the mandrel. In some instances, the first heat shrink tubeis comprised of one or more polymer resins, for example, a fluoropolymer such as the FluoroPEELZ® peelable heat shrink tubes, fluorinated ethylene propylene (FEP), etc. The first heat shrink tubecovers a region of the mandrelupon which the neural interface of the thin-film lead assembly is to be formed.

5 FIG.B 535 510 525 537 535 535 shows forming a first layer of polymer(e.g., a layer of the encapsulation layers) on the polymer tubeand the first heat shrink tubeto obtain a first intermediate structure. The first layer of polymermay be comprised of a medical grade polymer material. In some embodiments, the medical grade polymer is a thermosetting plastic or thermoplastic. For example, the medical grade polymer may be a soft polymer such as silicone, a polymer dispersion such as latex, a chemical vapor deposited poly(p-xylylene) polymer such as parylene, or a polyurethane such as Bionate® PCU or CarboSil® TSPCU. In certain instances, the first layer of polymeris polyurethane.

5 FIG.C 4 4 FIGS.A-F 540 400 537 540 542 543 542 545 550 535 510 542 535 510 543 545 555 560 543 535 525 543 535 525 shows a thin-film structure(e.g., the thin-film structuremay be obtained as discussed with respect to) being wrapped around the first intermediate structure. The thin-film structurecomprises a cable portionand a neural interface portion. The cable portioncomprises a supporting structureand conductive traces. The cable portion is helically wrapped around the first layer of polymerformed on the polymer tube. The helixes may be wrapped in a clockwise direction or anti-clockwise direction. In some instances, the cable portionis wrapped loosely around the first layer of polymerformed on the polymer tube. The “wrapped loosely” configuration means that the turns are loosely packed with an edge to edge distance of at least 0.5 mm between each turn of the helixes. The neural interface portioncomprises the supporting structure, wiring layer, one or more electrodes, and optional contacts (not shown). The neural interface portionis helically wrapped around the first layer of polymerformed on the heat shrink tube. The helixes may be wrapped in a clockwise direction or anti-clockwise direction. In some instances, the neural interface portionis wrapped tightly around the first layer of polymerformed on the heat shrink tube. The “wrapped tightly” configuration means that the turns are tightly packed with an edge to edge distance of less than 0.5 mm between each turn of the helixes.

5 FIG.D 5 FIG.D 565 542 540 565 565 543 540 565 560 570 565 543 540 572 570 shows forming a second layer of polymer(e.g., a layer of the encapsulation layers) on the cable portionof the thin-film structure. The second layer of polymermay be comprised of a medical grade polymer material. In some embodiments, the medical grade polymer is a thermosetting plastic or thermoplastic. For example, the medical grade polymer may be a soft polymer such as silicone, a polymer dispersion such as latex, a chemical vapor deposited poly(p-xylylene) polymer such as parylene, or a polyurethane such as Bionate® PCU or CarboSil® TSPCU. As shown, the second layer of polymeris not formed on the neural interface portionof the of the thin-film structuresuch that the second layer of polymerdoes not cover a top surface of the one or more electrodes.further shows a second heat shrink tubeplaced over the second layer of polymerand the neural interface portionof the of the thin-film structureto obtain a second intermediate structure. In some instances, the second heat shrink tubeis comprised of one or more polymer resins, for example, a fluoropolymer such as the FluoroPEELZ® peelable heat shrink tubes, FEP, etc.

5 FIG.E 572 525 543 540 570 542 540 543 540 565 542 535 565 542 543 572 572 525 570 535 565 shows the second intermediate structurebeing heated to: (i) heat shrink the first heat shrink tubeto define an inner diameter (i) of the neural interface portionof the thin-film structure, (ii) heat shrink the second heat shrink tubeto define a first outer diameter (o) of the cable portionof the thin-film structureand a second outer diameter (o′) of the neural interface portionof the thin-film structure(where the first outer diameter is greater than the second outer diameter because of the second layer of polymerformed over the cable portion), and (iii) at the same time melt and reflow (thermal reflow) the first layer of polymerand the second layer of polymerto encase completely or partially each of the cable portionand the neural interface portionin the polymer. The heating process may include baking the second intermediate structurein an oven, use of a heat gun, application of hot air, like methods, or any combination thereof. In some instances, the second intermediate structureis heated at 180° C. to 210° C., for example about 200° C., for 15 to 40 minutes, for example 25 minutes. In certain instances, the first heat shrink tubeand the second heat shrink tubeshrink or recover at a given temperature (e.g., about 200° C.) and the first layer of polymerand the second layer of polymerreflow at or about the same given temperature (e.g., about 200° C.).

572 525 520 543 570 535 565 570 542 543 535 565 542 540 540 542 535 543 540 540 543 565 543 572 525 570 520 575 5 FIG.F Consequently, as the second intermediate structureis heated to the given temperature, the first heat shrink tubemaintains its size (nowhere to shrink because it is wrapped onto the mandrel) and defines a smooth inner surface with a precisely controlled inner diameter (i) of the neural interface portion. Substantially simultaneously, the second heat shrink tubeshrinks (because at a same time/temperature the first layer of polymerand the second layer of polymerare liquefying allowing for the second heat shrink tubeto shrink) to define a smooth outer surface with a precisely controlled first outer diameter (o) of the cable portionand a precisely controlled second outer diameter (o′) of the neural interface portion. Substantially simultaneously, the first layer of polymerand the second layer of polymerliquefy and flow around the helically wrapped cable portionof the thin-film structure(the thin-film structuredoes not liquefy because it comprises a polymer (e.g., LCP) with a higher reflow temperature than the given temperature) and completely encase the cable portionwithin the polymer. Substantially simultaneously, the first layer of polymerliquefies and flows around the helically wrapped neural interface portionof the thin-film structure(the thin-film structuredoes not liquefy because it comprises a polymer (e.g., LCP) with a higher reflow temperature than the given temperature) and partially encases the neural interface portionwithin the polymer (only partially because the second layer of polymeris not formed over the neural interface portion, thus leaving exposed the top surface of the electrodes). Thereafter, the second intermediate structureis cooled (e.g., at ambient temperature), the first heat shrink tubeand the second heat shrink tubeare peeled away, and the mandrelis withdrawn to obtain the third intermediate structure, as shown in.

5 FIG.F 543 575 525 543 535 545 535 535 543 545 543 543 525 shows the neural interface portionof the third intermediate structurebeing unwrapped from the first heat shrink tube. The unwrapping process includes cutting through a portion of the neural interface portionto unwrap the polymer layers. In some instances, a laser is used to cut through the reflowed first layer of polymeralong a line defined by the supporting structure. In certain instances, the reflowed first layer of polymeris cut in such a manner that the reflowed first layer of polymerremains partially encasing the neural interface portionwithin the polymer (e.g., remains encasing at least the bottom and sides of the supporting structure). The unwrapping process includes separating the neural interface portionhelixes along the cut line and unwrapping the neural interface portionfrom the first heat shrink tube.

5 FIG.G 5 FIG.H 543 580 543 580 543 580 585 543 580 590 585 585 543 580 542 shows the unwrapped neural interface portionbeing rewrapped around a stent. The neural interface portionis helically wrapped around the stent. The helixes may be wrapped in a clockwise direction or anti-clockwise direction. In some instances, the neural interface portionis wrapped tightly around the stent. The “wrapped tightly” configuration means that the turns are tightly packed with an edge to edge distance of less than 0.5 mm between each turn of the helixes.shows a third heat shrink tubeplaced over the neural interface portionand the stentto obtain a fourth intermediate structure. In some instances, the thirst heat shrink tubeis comprised of one or more polymer resins, for example, a fluoropolymer such as the FluoroPEELZ® peelable heat shrink tubes, FEP, etc. The third heat shrink tubecovers the neural interface of the neural interface portionand the stent; whereas the cable portionremains uncovered.

5 FIG.I 5 FIG.J 543 590 585 580 535 580 543 590 543 590 585 535 543 590 585 580 535 580 580 590 500 shows the neural interface portionof the fourth intermediate structurebeing heated to: (i) heat shrink the third heat shrink tubeto compress the stentto a compressed configuration, and (ii) at the same time melt and reflow (thermal reflow) the first layer of polymerto encase completely or partially the stentin the polymer. The heating process may include baking the neural interface portionof the fourth intermediate structurein an oven, use of a heat gun, application of hot air, like methods, or any combination thereof. In some instances, the neural interface portionof the fourth intermediate structureis heated at 180° C. to 210° C., for example about 200° C., for 15 to 40 minutes, for example 25 minutes. In certain instances, the fourth heat shrink tubeshrinks or recovers at a given temperature (e.g., about 200° C.) and the first layer of polymerreflows at or about the same given temperature (e.g., about 200° C.). Consequently, as the neural interface portionof the fourth intermediate structureis heated to the given temperature, the third heat shrink tubeshrinks (because the stentcan compress under force) to define a compressed configuration with a precisely controlled outer diameter (o″). Substantially simultaneously, the first layer of polymerliquefies and flows around and through the mesh structure of the stentand completely or partially encases the stentwithin the polymer. Thereafter, the fourth intermediate structureis cooled (e.g., at ambient temperature) to obtain the thin-film lead assembly, as shown in. Optionally, the third heat shrink tube may be removed and the thin-film lead assembly may be inserted into a delivery device that maintains the neural interface portion and the stent in a compressed configuration.

While the manufacturing processes of a thin-film lead assembly and structures thereof have been described at some length and with some particularity with respect to a specific steps, it is not intended that the processes be limited to any such particular set of steps. Instead, it should be understood the manufacturing processes described herein are exemplary embodiments, and that the manufacturing processes are to be construed with the broadest sense to include variations of the steps to meet specific design and/or performance need described herein, as well as other variations that are well known to those of skill in the art. For example, the various intermediate and final structures described may be adjusted or modified with treatments to increase wettability of the thin-film lead assembly or to seal the ends of the lumens to meet specific design and/or performance needs. Furthermore, it is to be understood that other steps have been omitted from the description of the manufacturing processes for simplicity and clarity. The omitted steps may include obtaining or fabricating the polymer tubes, waiting predetermined amounts of time for curing or thermosetting, etc.

6 FIG. 6 FIG. 1 2 2 3 3 4 4 5 5 FIGS.,A,B,A,B,A-F, andA-J depicts a simplified flowchart depicting processing performed for accessing a site of a target biological structure in a patient and delivering a medical device or system for neurostimulation or interfacing to the site of the target biological structure according to various embodiments. As noted herein, the flowchart ofillustrates the architecture, functionality, and operation of possible implementations of systems, devices, and methods described with respect to. In this regard, each block in the flowchart or block diagrams comprises one or more processes or procedures. It should also be noted that, in some alternative implementations, the processes or procedures noted in each block may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and/or flowchart illustration, and combination of blocks in the block diagrams and/or flowchart illustration, can be implemented manually by a user such as a surgeon or by special purpose hardware-based systems that perform the specified functions or acts, or combinations of special purpose hardware and computer instructions stored on a non-transitory storage medium.

6 FIG. 7 FIG.A 605 705 710 715 700 715 705 700 705 715 705 705 710 715 705 705 shows a method of delivering a thin-film lead assembly to a target biological structure. At step, a thin-film lead assembly is placed within a delivery device (e.g., a delivery sheath) in a compressed configuration to deliver the thin-film lead assembly to a target biological structure. Alternatively, a medical device is obtain comprising the thin-film lead assembly predisposed within a delivery device (e.g., a delivery sheath) in a compressed configuration to deliver the thin-film lead assembly to a target biological structure. As shown in, the delivery deviceis configured to compress a portion of or the entire length the thin-film neural interfaceand the stent, which allows efficient delivery of the thin-film lead assemblyregardless of the orientation of the stent. In addition, use of the delivery devicecan prevent engagement/interfacing of the thin-film lead assemblywith tissue or bodily fluid until the delivery deviceis removed or the stentis deployed from the delivery device. The delivery devicemay comprise a removable material (e.g., peelable or absorbable material) that surrounds or covers at least the thin-film neural interfaceand the stent. In some instances, the delivery deviceis made from one or more of an implantable grade resorbable or non-resorbable polymer and/or metal material. In certain instances, the delivery devicecomprises one or more of polypropylene, polyester, nylon, polyether ether ketone (PEEK), polyurethane, polycarbonate, titanium, and stainless steel.

6 FIG. 7 FIG.A 7 FIG.B 7 FIG.A 7 FIG.B 610 615 720 700 725 730 700 715 735 700 725 740 700 620 700 705 735 700 740 725 710 715 715 745 With reference back to, at optional step, one or more incisions are made in a subject (e.g., a patient) to access a target biological structure. At step, the thin-film lead assembly is inserted and/or guided into a cavity of a body (optionally through the one or more incisions) to a target site of the biological system. As shown in, the cable portionof the thin-film lead assemblycomprises a lumenthat extends from a proximal endof the thin-film lead assemblythrough the stentto a distal endof the thin-film lead assembly. The lumenmay have a diameter wide enough to receive a guide wirefor guiding the thin-film lead assemblyto a target site of the biological system. At step, once the thin-film lead assembly reaches the target site of the biological system, the delivery device is retracted from at least the thin-film neural interface, and the stent is used to deploy the thin-film neural interface. A shown in, once the thin-film lead assemblyis at a target location, the delivery deviceis removed from the distal endof the thin-film lead assemblyand the guide wireis removed from the lumen. Thereafter, the thin-film neural interfaceis deployed using the stent. The deploying comprises expanding the stentfrom the compressed configuration () to an expanded configuration () that places the electrodesinto contact with the target biological structure (e.g., a blood vessel wall).

715 715 715 715 715 715 710 715 710 715 710 745 In some instances, the stentis deployed and expands automatically once the delivery device is retracted from the stent(e.g., once the compression force provided by the delivery device is removed, the stent automatically expands (for example, memory shape expansion)). In other instances, the stentis deployed and expands semi-automatically or manually once the delivery device is retracted from the stent(e.g., once the compression force provided by the delivery device is removed, the stent is expanded using one or more mechanism such as balloon assisted deployment). In some instances, the stentis deployed in a blood vessel and the stentis a cylindrical mesh tube such that blood flow is uninterrupted through the blood vessel. Advantageously, the helical wrapping of the thin-film neural interfacearound the stentallows for the thin-film neural interfaceto loosen and expand as the stentexpands. Morevoer, the “wrapped tightly” configuration means that the thin-film neural interfacecan support a dense arrangement electrodesfor interfacing consistently with the target biological structure.

6 FIG. 1 FIG. 625 630 With reference back to, at step, the thin-film lead assembly is connected to a computing device (e.g., a pulse generator or an interfacing processor). As described with respect to, the computing device can be implantable, semi-implantable, or an external system. At step, the neural interface is used to provide neurostimulation and/or sense electrical activity at the target biological structure.

While the invention has been described in detail, modifications within the spirit and scope of the invention will be readily apparent to the skilled artisan. It should be understood that aspects of the invention and portions of various embodiments and various features recited above and/or in the appended claims may be combined or interchanged either in whole or in part. In the foregoing descriptions of the various embodiments, those embodiments which refer to another embodiment may be appropriately combined with other embodiments as will be appreciated by the skilled artisan. Furthermore, the skilled artisan will appreciate that the foregoing description is by way of example only, and is not intended to limit the invention.